title: Atypical mitogen-activated protein kinase phosphatase implicated in regulating transition from pre-S-Phase asexual intraerythrocytic development of Plasmodium falciparum.
abstract: Intraerythrocytic development of the human malaria parasite Plasmodium falciparum appears as a continuous flow through growth and proliferation. To develop a greater understanding of the critical regulatory events, we utilized piggyBac insertional mutagenesis to randomly disrupt genes. Screening a collection of piggyBac mutants for slow growth, we isolated the attenuated parasite C9, which carried a single insertion disrupting the open reading frame (ORF) of PF3D7_1305500. This gene encodes a protein structurally similar to a mitogen-activated protein kinase (MAPK) phosphatase, except for two notable characteristics that alter the signature motif of the dual-specificity phosphatase domain, suggesting that it may be a low-activity phosphatase or pseudophosphatase. C9 parasites demonstrated a significantly lower growth rate with delayed entry into the S/M phase of the cell cycle, which follows the stage of maximum PF3D7_1305500 expression in intact parasites. Genetic complementation with the full-length PF3D7_1305500 rescued the wild-type phenotype of C9, validating the importance of the putative protein phosphatase PF3D7_1305500 as a regulator of pre-S-phase cell cycle progression in P. falciparum.
authors.affiliation: Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida, USA.
authors.forename: Bharath
authors.initials: B
authors.lastname: Balu
authors.forename: Christopher
authors.initials: C
authors.lastname: Campbell
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sedillo
authors.forename: Steven
authors.initials: S
authors.lastname: Maher
authors.forename: Naresh
authors.initials: N
authors.lastname: Singh
authors.forename: Phaedra
authors.initials: P
authors.lastname: Thomas
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Alena
authors.initials: A
authors.lastname: Pance
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Otto
authors.forename: Julian C
authors.initials: JC
authors.lastname: Rayner
authors.forename: John H
authors.initials: JH
authors.lastname: Adams
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D004474:Ecthyma, Contagious; D017125:Genes, Protozoan; D052940:Merozoites / Q000201:enzymology / Q000254:growth & development*; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016196:S Phase
chemical_list: D015800:Protozoan Proteins; D054639:Mitogen-Activated Protein Kinase Phosphatases